On optimal timing of antenatal corticosteroids : time to reformulate the question
- Author
- Isabelle Dehaene (UGent) , Johan Steen (UGent) , Oliver Dukes (UGent) , Camila Olarte Parra (UGent) , Kris De Coen (UGent) , Koenraad Smets (UGent) , Kristien Roelens (UGent) and Johan Decruyenaere (UGent)
- Organization
- Abstract
- Administration of antenatal corticosteroids (ACS) for accelerating foetal lung maturation in threatened preterm birth is one of the cornerstones of prevention of neonatal mortality and morbidity. To identify the optimal timing of ACS administration, most studies have compared subgroups based on treatment-to-delivery intervals. Such subgroup analysis of the first placebo-controlled randomised controlled trial indicated that a one to seven day interval between ACS administration and birth resulted in the lowest rates of neonatal respiratory distress syndrome. This efficacy window was largely confirmed by a series of subgroup analyses of subsequent trials and observational studies and strongly influenced obstetric management. However, these subgroup analyses suffer from a methodological flaw that often seems to be overlooked and potentially has important consequences for drawing valid conclusions. In this commentary, we point out that studies comparing treatment outcomes between subgroups that are retrospectively identified at birth (i.e. after randomisation) may not only be plagued by post-randomisation confounding bias but, more importantly, may not adequately inform decision making before birth, when the projected duration of the interval is still unknown. We suggest two more formal interpretations of these subgroup analyses, using a counterfactual framework for causal inference, and demonstrate that each of these interpretations can be linked to a different hypothetical trial. However, given the infeasibility of these trials, we argue that none of these rescue interpretations are helpful for clinical decision making. As a result, guidelines based on these subgroup analyses may have led to suboptimal clinical practice. As an alternative to these flawed subgroup analyses, we suggest a more principled approach that clearly formulates the question about optimal timing of ACS treatment in terms of the protocol of a future randomised study. Even if this 'target trial' would never be conducted, its protocol may still provide important guidance to avoid repeating common design flaws when conducting observational 'real world' studies using statistical methods for causal inference.
- Keywords
- Obstetrics and Gynecology, General Medicine, Preterm birth, Antenatal corticosteroids, Clinical decision support, Causal inference, RESPIRATORY-DISTRESS-SYNDROME, RANDOMIZED-TRIALS, TARGET TRIAL, EXPOSURE, INTERVAL, THERAPY, MORTALITY, DELIVERY, MODELS, BIRTH
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01GV5FCTW9XJTN8WFYTPBQMGGH
- MLA
- Dehaene, Isabelle, et al. “On Optimal Timing of Antenatal Corticosteroids : Time to Reformulate the Question.” ARCHIVES OF GYNECOLOGY AND OBSTETRICS, vol. 308, no. 4, 2023, pp. 1085–91, doi:10.1007/s00404-023-06941-w.
- APA
- Dehaene, I., Steen, J., Dukes, O., Olarte Parra, C., De Coen, K., Smets, K., … Decruyenaere, J. (2023). On optimal timing of antenatal corticosteroids : time to reformulate the question. ARCHIVES OF GYNECOLOGY AND OBSTETRICS, 308(4), 1085–1091. https://doi.org/10.1007/s00404-023-06941-w
- Chicago author-date
- Dehaene, Isabelle, Johan Steen, Oliver Dukes, Camila Olarte Parra, Kris De Coen, Koenraad Smets, Kristien Roelens, and Johan Decruyenaere. 2023. “On Optimal Timing of Antenatal Corticosteroids : Time to Reformulate the Question.” ARCHIVES OF GYNECOLOGY AND OBSTETRICS 308 (4): 1085–91. https://doi.org/10.1007/s00404-023-06941-w.
- Chicago author-date (all authors)
- Dehaene, Isabelle, Johan Steen, Oliver Dukes, Camila Olarte Parra, Kris De Coen, Koenraad Smets, Kristien Roelens, and Johan Decruyenaere. 2023. “On Optimal Timing of Antenatal Corticosteroids : Time to Reformulate the Question.” ARCHIVES OF GYNECOLOGY AND OBSTETRICS 308 (4): 1085–1091. doi:10.1007/s00404-023-06941-w.
- Vancouver
- 1.Dehaene I, Steen J, Dukes O, Olarte Parra C, De Coen K, Smets K, et al. On optimal timing of antenatal corticosteroids : time to reformulate the question. ARCHIVES OF GYNECOLOGY AND OBSTETRICS. 2023;308(4):1085–91.
- IEEE
- [1]I. Dehaene et al., “On optimal timing of antenatal corticosteroids : time to reformulate the question,” ARCHIVES OF GYNECOLOGY AND OBSTETRICS, vol. 308, no. 4, pp. 1085–1091, 2023.
@article{01GV5FCTW9XJTN8WFYTPBQMGGH, abstract = {{Administration of antenatal corticosteroids (ACS) for accelerating foetal lung maturation in threatened preterm birth is one of the cornerstones of prevention of neonatal mortality and morbidity. To identify the optimal timing of ACS administration, most studies have compared subgroups based on treatment-to-delivery intervals. Such subgroup analysis of the first placebo-controlled randomised controlled trial indicated that a one to seven day interval between ACS administration and birth resulted in the lowest rates of neonatal respiratory distress syndrome. This efficacy window was largely confirmed by a series of subgroup analyses of subsequent trials and observational studies and strongly influenced obstetric management. However, these subgroup analyses suffer from a methodological flaw that often seems to be overlooked and potentially has important consequences for drawing valid conclusions. In this commentary, we point out that studies comparing treatment outcomes between subgroups that are retrospectively identified at birth (i.e. after randomisation) may not only be plagued by post-randomisation confounding bias but, more importantly, may not adequately inform decision making before birth, when the projected duration of the interval is still unknown. We suggest two more formal interpretations of these subgroup analyses, using a counterfactual framework for causal inference, and demonstrate that each of these interpretations can be linked to a different hypothetical trial. However, given the infeasibility of these trials, we argue that none of these rescue interpretations are helpful for clinical decision making. As a result, guidelines based on these subgroup analyses may have led to suboptimal clinical practice. As an alternative to these flawed subgroup analyses, we suggest a more principled approach that clearly formulates the question about optimal timing of ACS treatment in terms of the protocol of a future randomised study. Even if this 'target trial' would never be conducted, its protocol may still provide important guidance to avoid repeating common design flaws when conducting observational 'real world' studies using statistical methods for causal inference.}}, author = {{Dehaene, Isabelle and Steen, Johan and Dukes, Oliver and Olarte Parra, Camila and De Coen, Kris and Smets, Koenraad and Roelens, Kristien and Decruyenaere, Johan}}, issn = {{0932-0067}}, journal = {{ARCHIVES OF GYNECOLOGY AND OBSTETRICS}}, keywords = {{Obstetrics and Gynecology,General Medicine,Preterm birth,Antenatal corticosteroids,Clinical decision support,Causal inference,RESPIRATORY-DISTRESS-SYNDROME,RANDOMIZED-TRIALS,TARGET TRIAL,EXPOSURE,INTERVAL,THERAPY,MORTALITY,DELIVERY,MODELS,BIRTH}}, language = {{eng}}, number = {{4}}, pages = {{1085--1091}}, title = {{On optimal timing of antenatal corticosteroids : time to reformulate the question}}, url = {{http://doi.org/10.1007/s00404-023-06941-w}}, volume = {{308}}, year = {{2023}}, }
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